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Neuroplastic changes associated to antidepressant efficacy after a short treatment with a 5-HT4 receptor agonist

AuthorsPascual-Brazo, Jesús ; Pilar-Cuéllar, Fuencisla ; Ruiz, I.; Martín, Alicia ; Pazos, Ángel ; Valdizán, Elsa M. ; Vidal, Rebeca ; Castro, Elena
Issue Date2009
PublisherSociety for Neuroscience
CitationNeuroscience 2009
AbstractThe 5-HT4 receptor agonist RS67333 has been recently proposed to possess antidepressant-like properties in rats after a treatment of only 3 days of duration. This result suggest a new strategic therapy for depressive disorders with a short onset of action. It has been described that certain hippocampal neuroplastic changes induced by classical antidepressants, as the increase in hippocampal BDNF levels or in the number of new neurons generated in the dentate gyrus, occur only after several weeks of treatment. Here, immunohistochemical and in situ hybridization studies have carried out in order to assess if a 3-days treatment with this 5-HT4 receptor agonist induces neuroplastic changes comparable to those observed after several weeks of treatment with typical antidepressants. RS67333 (1,5 mg/kg/day) was delivered s.c. through 3-days osmotic minipumps to male Sprague-Dawley rats. RS67333 administration for 3 days increases the expression of the neurotrophic factor BDNF mRNA in hippocampus (CA3 field 28,2% Student-t test unpaired data, p<0,01) measured by in situ hybridization. BrdU immunohistochemistry revealed that a 3-days regime with RS67333 upregulates the proliferation rate of adult hippocampal progenitors a 19,3 % (p<0,05) and the number of β-catenin-immunopositive cells in the dentate gyrus a 25,2 % (p<0,05). Moreover, when the identity of β-catenin positive neural progenitors was analyzed by colocalization with Sox2 and GFAP, RS67333 increased specifically the number of hippocampal amplifying adult progenitors expressing β-catenin, suggesting that this treatment could be targeting the same type of neural progenitors that the classical antidepressants. These findings suggest that a 3-day treatment with RS67333 induces the same type of neuroplastic changes that require several weeks for classical antidepressants. They support the relevance of 5-HT4 receptor agonists as candidates for a new class of antidepressant response with a short onset of action.
DescriptionTrabajo presentado al 39th annual meeting of Neuroscience celebrado en Chicago del 17 al 21 de octubre de 2009.
Appears in Collections:(IBBTEC) Comunicaciones congresos
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